For the first aim, we have made progress in the following three areas. 1. Indirect calorimeters are gold-standard measurements of energy expenditure. However, standard measurements using metabolic carts limit to only short time measurements such as 30-minute basal or exercise conditions. Whole-room calorimeters (respiration chambers) expand our ability to study humans in near free-living conditions and allow us to separate out different components of energy expenditure (e.g., sleeping vs. resting, activity vs. postprandial). The major limitation of the chambers is the larger size (20-30 m3) reduces its sensitivity and response time, and allows environmental artifacts. We have been systematically evaluating our whole-room indirect calorimetry chamber systems since their inception (2008) and through a series of modifications we performed in FY 2011. We measured specific impacts from inlet air supply, outgoing flow characteristics, temperature, humidity, and filtering on the measurements of oxygen and carbon dioxide. Ultimately, we are using this knowledge to optimize the chamber performances (accuracy, precision, and response time). The data will be presented at the 2nd international conference on Recent Advances and Controversies in Measuring Energy Metabolism (Nov 2-4, Maastricht, The Netherlands). 2. For accurate free-living physical activity measurements, portable accelerometers are the gold-standard objective technique. This is a fast-developing field, both in sensor designs and in data analyses. We developed a universal calibrator from a standard bench-top orbital shaker, and evaluated the technical and field applicability of two new generation physical activity monitors (Actigraph GT3X+ and GENEActive G3) for the National Health and Nutrition Examination Survey (NHANES 2011-12) study. We designed specific metrics for studying the properties of these monitors for the NHANES field applications, while drawing experiences and expertise from our previous work with sensor designs (Chen et al. 2011), model development (Van Hees et al. 2011), and analysis of the NHANES field data from 2003-2006 (Bankoski et al. 2011). Working closely with our NCI and NHANES collaborators, we selected the monitor that met the major needs of NHANES, and has been working on continue evaluation the monitor (1800 units in the field) and quality control during the 2-year data collection process. 3. We continue to work with our Iceland and NIA investigators on the free-living physical activity and sleep assessment data we collected for the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study from March 2009 to July 2010. We have cleaned the activity and sleep data, extracted parameters relevant to metabolic health and function, such as total amount of physical activity and moderate to vigorous activity times. We are analyzing these parameters with combined measures from the large database such as cardiovascular health, bone and muscle, metabolism, and cognitive function. Two manuscripts are in preparations. For the second aim, we made every effort in recruiting study volunteers for the clinical protocol titled Diet-Induced-Obesity Resistant Phenotypes in Humans (09-DK-0238), with the goal of identifying healthy lean subjects who are resistant (gain less than 25% of weight as predicted) to hypercaloric diets for 4 weeks (+1000 kcal/day over weight balanced diets). During FY11, we have phone-screened 32 potential volunteers (referred either by NIH Patient Recruitment office, flyers, word of mouth, or by direct contact). We consented 4 subjects for outpatient screening, and two study volunteers have enrolled. Unfortunately, both subject decided to withdraw voluntarily after the first week of study, one due to dietary noncompliance issue, and the other had a family death. The major factor impacted accrual has been the commitment to the study length (5 weeks of inpatient study + one month run-in period). After discussions with our Branch Chief Dr. Marc Reitman, we decided to temporarily halt further recruitment of new study volunteers and reevaluate the protocol. We have developed a new clinical protocol titled Energy expenditure responses to a range of environmental temperatures around the thermal neutral zone, which is the temperature region where heat production (energy expenditure)is a minimum and does not vary with environmental temperature. Surprisingly, little is understood about how the body regulates heat production (and thus energy expenditure) in response to subtle changes in environmental temperature and about the population variation in these processes. It is plausible that the mechanisms governing heat production contribute to regulation of body weight. Thus understanding these control mechanisms should provide insight into the pathophysiology underlying the current epidemic of obesity. The primary goals of this study are to develop metrics to study resting energy expenditure responses to change in temperature, both cold and hot, and establish the ranges of such responses in normal lean and obese, young and old, women and men. While this topic has interested many over decades, we were unaware of detailed data in heat and energy balances over multiple temperature points and in different subject populations. We plan to start the protocol in FY12.